Ketotifen in the Prophylaxis of Extrinsic Bronchial Asthma: Discussion
Ketotifen (Zaditen or Zasten) is a benzocylohepta-thiophene derivation that is orally active; it is metabolized in humans to the glucuronide and desmethyl derivatives, both of which are excreted in the urine. Clinical studies have shown ketotifen to be effective in the treatment of asthma when compared with placebo, theophylline, and cromoglycate, and to have steroid-sparing effects. Ketotifen inhibits eosinophil activation and accumulation* and diminishes development of airway hyperreactivity. It is widely held that asthmatic airways become hyperreactive as a consequence of inflammatory events in which eosinophils predominate; hence, these properties of ketotifen may be expected to confer efficacy in the treatment and prevention of asthma and allergic reactions. Ketotifen has also been shown to preempt the hyposensitivity that often follows regular use of P-adrenergic agonists. buy mircette online
This property has been attributed to an effect of ketotifen on p-adrenergic receptor expression but may alternatively be attributed to diminution of airway hyperreactivity, since ketotifen inhibits development of hypersensitivity due to (±) isoprenaline, as well as platelet-activating factor and allergen. It also potently inhibits pathologic reactions initiated by platelet-activating factor in pulmonary tissue. Ketotifen is a potent noncompetitive antagonist of histamine (HJ responses; however, such a property does not confer antiasthmatic efficacy, but rather serves as symptomatic therapy in allergy.
In the present study the symptoms and findings in patients with mild asthma were significantly improved by 2 mg of the slow-release oral formulation of ketotifen, compared to a placebo. At the end of treatment, the efficacy of the active drug was significantly higher than overall efficacy of the placebo, since 76 percent (versus 30 percent) of the patients had a good or very good response. This rate of success is of the same order as that observed in trials using 1 mg of ketotifen twice per day. It compares with that of cromolyn sodium, the other widely used drug in the prevention of bronchial asthma, for which an overall clinical efficacy of 77 percent has been reported. Another way of revealing the effectiveness of prophylactic therapy is to monitor daily usage of other antiasthmatic drugs (eg, inhaled P-sympathomimetics or steroid aerosols) necessary for the control of this disease.